Decentralized and centralized supply chains with trade credit option

The notion of a trade credit period is a common business practice, where a supplier allows a buyer a specified period to make a payment in full for a purchase made. The objective of this thesis is to explore the role of such a credit payment option in supply chain management. Towards this end, a two-echelon supply chain, consisting of a single supplier (e.g. manufacturer) and the cases of both a single and multiple buyers (e.g. retailers) is examined under decentralized (independent) and centralized (coordinated) decision making scenarios. The major emphasis of this research is limited to the case of a single product with price-sensitive deterministic, as well as stochastic market demand.The conditions under which a trade credit period should be offered and its appropriate length are determined from the supplier’s perspective under the decentralized case. Under the centralized decision scenario, the efficacy of a trade credit policy as a supply chain coordination mechanism is thoroughly analyzed and guidelines for pricing, production and delivery decisions are developed. The concepts developed in this study are illustrated via a number of numerical examples, in conjunction with thorough sensitivity analyses involving some selected problem parameters.The major contribution of this thesis is that we incorporate the pricing and inventory issues in supply chains with an endogenous credit payment period. This is the first study that examines the efficacy of trade credit option as a coordination mechanism. We propose a coordination mechanism that coordinates the supply chain, when a trade credit by itself is not sufficient to serve such a purpose, while preserving the benefits of a trade credit option. Also, this study is the first to examine the issues concerning trade credit under price sensitive stochastic demand. Another first for this work is the exploration of the implications of a trade credit policy in supply chains consisting of multiple competing retailers. The effects of the extent of competition and the market size on trade credit policy are evaluated. Our analyses lead to some important practical implications, to serve as managerial guidelines.Ph.D., Decision Sciences -- Drexel University, 201

A Thiazole Orange Derivative Targeting the Bacterial Protein FtsZ Shows Potent Antibacterial Activity.

The prevalence of multidrug resistance among clinically significant bacteria calls for the urgent development of new antibiotics with novel mechanisms of action. In this study, a new small molecule exhibiting excellent inhibition of bacterial cell division with potent antibacterial activity was discovered through cell-based screening. The compound exhibits a broad spectrum of bactericidal activity, including the methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus and NDM-1 Escherichia coli. The in vitro and in vivo results suggested that this compound disrupts the dynamic assembly of FtsZ protein and Z-ring formation through stimulating FtsZ polymerization. Moreover, this compound exhibits no activity on mammalian tubulin polymerization and shows low cytotoxicity on mammalian cells. Taken together, these findings could provide a new chemotype for development of antibacterials with FtsZ as the target

Maternal exposure to life events during pregnancy and congenital heart disease in offspring: a case-control study in a Chinese population

Background: Previous studies have suggested that maternal stress could increase the risk of some adverse pregnancy outcomes, but evidence on congenital heart disease (CHD) is limited. We aimed to explore the association between maternal exposure to life events during pregnancy and CHD in offspring. Methods: The data was based on an unmatched case-control study about CHD conducted in Shaanxi province of China from 2014 to 2016. We included 2280 subjects, 699 in the case group and 1581 in the control group. The cases were infants or fetuses diagnosed with CHD, and the controls were infants without any birth defects. The life events were assessed by the Life Events Scale for Pregnant Women, and were divided into positive and negative events for synchronous analysis. A directed acyclic graph was drawn to screen the confounders. Logistic regression was employed to estimate the odds ratio and 95% confidence interval for the effects of life events on CHD. Results: After controlling for the potential confounders, the pregnant women experiencing the positive events during pregnancy had lower risk of CHD in offspring than those without positive events (OR = 0.38, 95%CI: 0.30 ~ 0.48). The risk of CHD in offspring could increase by 62% among the pregnant women experiencing the negative events compared to those without (OR = 1.62, 95%CI: 1.29 ~ 2.03). Both effects showed a certain dose-response association. Besides, the positive events could weaken the risk impact of negative events on CHD. Conclusion: It may suggest that maternal exposure to negative life events could increase the risk of CHD in offspring, while experiencing positive events could play a potential protective role

Tuning the Framework Formation of Silver(I) Coordination Architectures with Heterocyclic Thioethers

The reactions of a series of nitrogen-containing heterocyclic thioether ligands, 2,2Ј-[methylenebis (thio) , with silver() nitrate or silver() perchlorate salt led to the formation of five new metal-organic supramolecular architectures from dinuclear to threedimensional structures. All the structures were determined by single-crystal X-ray diffraction analysis. In the crystal structures of the five complexes, a variety of coordination modes of Ag I have been observed, probably due to the variation of the chain length of the linker unit or the terminal groups as well as the counter anions, which indicates that the nature of the ligands is a determining factor in controlling the structural topologies of such metal-organic supramolecular architectures. Geometrical effects seem to be more important than electronic effects in these systems, leading the Ag I centre to prefer to coordinate to N donors first rather than S donors despite Ag I being a 'soft' metal

Broad-Spectrum Profiling of Drug Safety via Learning Complex Network.

Drug safety is a severe clinical pharmacology and toxicology problem that has caused immense medical and social burdens every year. Regretfully, there still misses a reproducible method to assess drug safety systematically and quantitatively. In this study, we developed an advanced machine learning model for de novo drug safety assessment by solving the multilayer drug-gene-adverse drug reaction (ADR) interaction network. For the first time, the drug safety was assessed in a broad landscape of 1,156 distinct ADRs. We also designed a parameter ToxicityScore to quantify the overall drug safety. Moreover, we determined association strength for every 3,807,631 gene-ADR interactions, which clues mechanistic exploration of ADRs. For convenience, we deployed the model as a web service ADRAlert-gene at http://www.bio-add.org/ADRAlert/. In summary, this study offers insights into prioritizing safe drug therapy. It helps to reduce the attrition rate of new drug discovery by providing reliable ADR profile in early pre-clinical stage

Study of Benzofuroquinolinium Derivatives as a New Class of Potent Antibacterial Agent and the Mode of Inhibition Targeting FtsZ

New generation of antibacterial agents are urgently needed in order to fight the emergence of multidrug-resistant bacteria. FtsZ is currently identified as a promising target for new types of antimicrobial compounds development because of its conservative characteristics and its essential role played in bacterial cell division. In the present study, the antibacterial activity of a series of benzofuroquinolinium derivatives was investigated. The results show that the compounds possess potent antibacterial activity against drug resistant pathogens including MRSA, VREF and NDM-1 Escherichia coli. Biological studies reveal that the compound is an effective inhibitor that is able to suppress FtsZ polymerization and GTPase activity and thus stopping the cell division and causing cell death. More importantly, this series of compounds shows low cytotoxicity on mammalian cells and therefore they could be new chemotypes for the development of new antibacterial agents targeting the cell-division protein FtsZ

Genome-Wide Association Study in Asian Populations Identifies Variants in ETS1 and WDFY4 Associated with Systemic Lupus Erythematosus

Systemic lupus erythematosus is a complex and potentially fatal autoimmune disease, characterized by autoantibody production and multi-organ damage. By a genome-wide association study (320 patients and 1,500 controls) and subsequent replication altogether involving a total of 3,300 Asian SLE patients from Hong Kong, Mainland China, and Thailand, as well as 4,200 ethnically and geographically matched controls, genetic variants in ETS1 and WDFY4 were found to be associated with SLE (ETS1: rs1128334, P = 2.33×10−11, OR = 1.29; WDFY4: rs7097397, P = 8.15×10−12, OR = 1.30). ETS1 encodes for a transcription factor known to be involved in a wide range of immune functions, including Th17 cell development and terminal differentiation of B lymphocytes. SNP rs1128334 is located in the 3′-UTR of ETS1, and allelic expression analysis from peripheral blood mononuclear cells showed significantly lower expression level from the risk allele. WDFY4 is a conserved protein with unknown function, but is predominantly expressed in primary and secondary immune tissues, and rs7097397 in WDFY4 changes an arginine residue to glutamine (R1816Q) in this protein. Our study also confirmed association of the HLA locus, STAT4, TNFSF4, BLK, BANK1, IRF5, and TNFAIP3 with SLE in Asians. These new genetic findings may help us to gain a better understanding of the disease and the functions of the genes involved